Abstract:
:Decyl and phenyl disulfide derivatives of 6-mercaptopurine and 6-thioguanine (6-TG) were examined for antineoplastic activity under aerobic and hypoxic conditions toward EMT6 cells in culture. Although these derivatives did not display selective toxicity toward the hypoxic cells, they were significantly more toxic than 6-TC to this cell line at 500 microM after a 2-h exposure. In conjunction with this cytotoxicity, these agents were found to deplete the cellular glutathione (GSH) levels to varying degrees at this same concentration after a 1-h period. Therefore, the effect of modulating the cellular GSH on the cytotoxicity of these agents was investigated. When the GSH was depleted to less than 5 or 41% of control levels, the cytotoxicity exhibited by these agents was significantly increased while that of 6-TG remained unchanged. The cytotoxicity of these agents was similar to that of decanethiol and thiophenol, the thiol portion of the molecules, both under normal treatment conditions or after depletion of GSH. The lack of selective toxicity toward hypoxic cells was correlated to the finding that the disulfides were broken down to the parents, 6-mercaptopurine, and 6-TG, by cells under aerobic conditions. However, these studies demonstrate that manipulation of GSH levels might yield a therapeutic gain for these disulfide derivatives of antitumor agents.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kirkpatrick DLsubject
Has Abstractpub_date
1987-08-15 00:00:00pages
4391-5issue
16eissn
0008-5472issn
1538-7445journal_volume
47pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The development of androgen-independent growth in advanced carcinoma of the prostate (CaP) is associated with poor prognosis and few therapeutic options. Chemotherapeutic drugs offer the afflicted patient palliative benefits, but these are short-lived because of the chemoresistant nature of hormone-refractory prostate...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1612
更新日期:2004-11-15 00:00:00
abstract::Proteasome inhibitors such as bortezomib exhibit clinical efficacy in multiple myeloma, but studies in acute myeloid leukemia (AML) have been disappointing to date. The apparent failure in AML likely reflects a lack of biological understanding that might clarify applications of proteosome inhibitors in this disease. H...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-3018
更新日期:2011-03-01 00:00:00
abstract::The expression of human leukocyte antigen (HLA) class I alleles was analyzed in 65 renal cell carcinomas using one-dimensional isoelectric focusing. Normal organ tissue and peripheral blood lymphocytes were used as controls. The patients were serologically typed using the standard microcytotoxicity test. Forty-two pat...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-02-15 00:00:00
abstract::The growth of human melanoma cells FO-1 in nude mice is strongly inhibited or even abrogated when the cells are stably transfected with a plasmid expressing an antisense RNA to the insulin-like growth factor 1 receptor (IGF-1R) RNA, which causes a marked reduction in the number of IGF-1 receptors. When a tumor arises ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-09-15 00:00:00
abstract::To elicit specific cellular immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the MHC class I pathway constitutes a central issue. We report here a novel formula of hydrophobized polysaccharide nanoparticles, which can deliver a HER2 oncoprotein containing an ep...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::Anguidine is a fungal metabolite with antitumor activity in a murine colon cancer model. Because of disappointing results in clinical trials, we analyzed the lethal and cytokinetic effects of anguidine on cultured human colon cancer cells. The studies revealed a moderate reduction in survival only after prolonged drug...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-10-01 00:00:00
abstract::Despite studies that show the antitumor activity of Hsp90 inhibitors, such as geldanamycin (GA) and its derivative 17-allylamino-demethoxygeldanamycin (17-AAG), recent reports indicate that these inhibitors lack significant single-agent clinical activity. Resistance to Hsp90 inhibitors has been previously linked to ex...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5175
更新日期:2008-09-15 00:00:00
abstract::Fluence response relationships for the induction of DNA damage in the skin of UV-irradiated Xiphophorus fish were obtained by quantitative gel electrophoresis of unlabeled DNA following extraction and treatment with an enzyme preparation that makes single strand breaks next to cyclobutane pyrimidine dimers. A buffer c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-05-15 00:00:00
abstract::Morphine is used to treat pain in several medical conditions including cancer. Here we show that morphine, in a concentration typical of that observed in patients' blood, stimulates human microvascular endothelial cell proliferation and angiogenesis in vitro and in vivo. It does so by activating mitogen-activated prot...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract::Alkyl-lysophospholipids have been shown to possess antitumoral activity in animal and in human tumors. Among them, racemic 1-O-octadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OCH3) had an antimetastatic effect in experimental tumors. We investigated the effect of ET-18-OCH3 on invasion of MO4 mouse fibrosarcoma ce...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Retinoic acid (RA)-treated HL-60 cells were used as a model to study differentiation of granulocytic leukemias. RA induces these cells to mature into granulocytes and to decrease growth. Mediators of these RA effects have not been identified definitively, but transforming growth factor-beta (TGF-beta) has been implica...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::The Rb/E2F pathway is deregulated in most human brain tumors, and the finding that loss of E2F1 reduced pituitary tumorigenesis in Rb(+/-) mice suggests that loss of pRb induces brain tumors by activating E2F1. We therefore investigated the role of E2F1 in the development and maintenance of brain cancer using a transg...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-2973
更新日期:2007-05-01 00:00:00
abstract::Alteration of the phenotype of breast cancers from estrogen-dependent to estrogen-independent growth often leads to the failure of antiestrogenic tumor therapies. We report that overexpression of vascular endothelial growth factor (VEGF) by estrogen-dependent MCF-7 breast cancer cells could abolish estrogen-dependent ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-08-01 00:00:00
abstract::Transcription factor p53 and phosphatase PTEN are two tumor suppressors that play essential roles in suppression of carcinogenesis. However, the mechanisms by which p53 mediates anticancer activity and the relationship between p53 and PTEN are not well understood. In the present study, we found that pretreatment of mo...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-4184
更新日期:2005-08-01 00:00:00
abstract::We demonstrated previously elevated caveolin-1 expression in metastatic mouse and human prostate cancer cells both in vitro and in vivo. In this study, we analyzed its prognostic value for progression of clinically confined human prostate cancer. Immunohistochemical staining with a caveolin-1-specific antibody was per...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-11-15 00:00:00
abstract::Trans-3,4',5-trihydroxystilbene (resveratrol), a phytoalexin present in grapes and grape products such as wine, has been identified as a chemopreventive agent. Recent studies performed with MCF-7 human breast cancer cells have demonstrated superestrogenic effects with resveratrol. In contrast, studies performed using ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-10-15 00:00:00
abstract::Single-chain antigen-binding proteins, or sFvs, represent potentially unique molecules for targeted delivery of drugs, toxins, or radionuclides to a tumor site. In previous studies (Cancer Res., 51:6363-6371, 1991) using a human colon carcinoma xenograft model, it was demonstrated that the sFv has an extremely rapid p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-06-15 00:00:00
abstract::Spy1A is a unique cell cycle activator known to mediate cell cycle progression and override the DNA damage response. This study focused on determining the role of this protein on postnatal mammary gland morphogenesis and neoplasia. Herein, we show that Spy1A levels are tightly regulated during mammary gland developmen...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6453
更新日期:2008-05-15 00:00:00
abstract::Targeted therapies for cancer are inherently limited by the inevitable recurrence of resistant disease after initial responses. To define early molecular changes within residual tumor cells that persist after treatment, we analyzed drug-sensitive lung adenocarcinoma cell lines exposed to reversible or irreversible epi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2668
更新日期:2011-07-01 00:00:00
abstract::Peroxisome proliferator-activated receptor (PPAR) gamma is an important signaling molecule in cells of mesenchymal origin, inducing differentiation and regulating cell proliferation in several cell types such as vascular smooth muscle cells. Leiomyomas arise from smooth muscle cells of the uterine myometrium with an i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-03-15 00:00:00
abstract::The nevoid basal cell carcinoma (Gorlin) syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple developmental defects and cancer susceptibility, in particular to basal cell carcinoma. The human homologue of Drosophila patched (PTCH) was recently identified, mapped to the NBCCS locus on chromosome...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-10-15 00:00:00
abstract::Gene amplification is an important mechanism of increased gene expression in a number of human solid tumors. We have recently identified and cloned sequences from a novel DNA amplification unit in malignant fibrous histiocytoma. The amplified sequences are derived from chromosome 12q13-14 and encode a gene designated ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::Successful treatment of many patients with osteosarcoma requires more effective chemotherapy. Since new agents are needed, we have developed an immunotoxin using TP-3, an IgG2b mAb which recognizes human and canine osteosarcomas and budding capillaries of tumors. The plant hemitoxin, pokeweed antiviral protein (PAP), ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-03-15 00:00:00
abstract::Black cohosh is an herbal extract that is often used as an alternative to estrogen-based replacement therapies to treat hot flushes that frequently accompany the transition to menopause. Although cancer-free women as well as breast cancer patients and survivors use black cohosh to relieve vasomotor symptoms, there is ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-1812
更新日期:2008-10-15 00:00:00
abstract::Neurofibromatosis type 2 (NF2) is a dominantly inherited cancer disorder caused by mutations at the NF2 gene locus. Merlin, the protein product of the NF2 gene, has been shown to negatively regulate Rac1 signaling by inhibiting its downstream effector kinases, the p21-activated kinases (Pak). Given the implication of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0866
更新日期:2008-10-01 00:00:00
abstract::The DNA intercalator, 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and the nonintercalator, etoposide (VP-16) produce topoisomerase II-mediated protein-linked DNA strand breaks. This function of topoisomerase II was investigated in relation to cell proliferation and cell cycle. Mouse fibroblasts NIH 3T3 and...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-04-15 00:00:00
abstract::We report that tumor necrosis factor (TNF) alpha induced a strong antitumor immune reaction when it was produced in arteries leading to tumors by gene transfer in vivo. We used a mouse model carrying a sarcoma-180 tumor in the right footpad and injected the fusogenic liposomes encapsulating the human TNF-alpha gene in...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-12-15 00:00:00
abstract::Brca2 is an important tumor suppressor associated with susceptibility to breast cancer. Although increasing evidence indicates that the primary function of Brca2 is to facilitate the repair of DNA damage via the homologous recombination pathway, how Brca2 prevents breast cancer is largely unknown. To study the role of...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-2270
更新日期:2004-03-15 00:00:00
abstract::3-(Iodoacetamido)-benzoylurea (3-IAABU) is a newly synthesized antitubulin compound with a molecular weight of 347. 3-IAABU exhibited anticancer activity in a variety of tumor cell lines with ID90 in the range of 0.015-0.29 microM for leukemic cells and 0.06-0.92 microM for solid tumors. Higher selectivity against mal...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::Many epithelial tumors show deletion of the short arm of chromosome 8 that is related to aggressive disease or adverse prognosis. In undissected samples of urothelial cell carcinoma of the bladder, at least two regions of loss of heterozygosity (LOH) were identified previously within a small region of 8p11-p12. LOH an...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00